One goal of this proposal is to study the alteration of the regulation of cellular DNA synthesis in SV40 transformed cells and to characterize the infected but non-transformed cells. We propose to isolate a polyploid cell population(s) which is induced 24-48 hours post-infection and determine the relationship of these polyploid cells to transformation with SV40 virus. The system we propose to use is a contact inhibited Chinese hamster cell strain. We have previously shown this cell strain to be 1) diploid, 2) nonpermissive to complete virus replication, 3) highly susceptible to SV40 infection (approximately 100 percent of the cells are infected), and 4) approximately 0.1-5 percent of the cells are transformed. The infected but non-transformed cells will be isolated, biologically characterized and studied in relation to their susceptibility to transformation by other carcinogenic agents. Another cell model which we have developed will be of interest in the study of the expression of the SV40 genome in differentiated and undifferentiated cells. We have adapted the stem cell, embryonal carcinoma, of a spontaneous testicular teratocarcinoma to in vitro culture conditions. The embryonal carcinoma retains the potential to differentiate in vitro and in vivo. We have shown that SV40 and polyoma viruses are capable of infecting the differentiated cells, but are not capable of infecting the undifferentiated cell, embryonal carcinoma. Further studies are planned to characterize this response of murine teratocarcinoma to DNA and RNA viruses. BIBLIOGRAPHIC REFERENCES: Shartzendruber, D.E. and Lehman, J.M.: Neoplastic differentiation: Interaction of Simian virus 40 and polyoma virus with murine teratocarcinoma cells in vitro. J. Cell Physiol. 85: 179-188, 1975. Caltrider, N. and Lehman, J.M.: Changes in lactate dehydrogenase enzyme pattern in Chinese hamster cells infected and transformed with SV40 virus. Cancer Res. 35: 1944-1949, 1975.